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NEW ONSET FATIGUE AND WEAKNESS IS A SIGN OF BILIARY SEPSIS AND SEVERE BILIARY INFECTION
Kara Faktor*1, Lygia Stewart1,2
1Department of Surgery, University of California San Francisco, San Francisco, CA; 2San Francisco VA Health Care System, San Francisco, CA

Background: Our group has a long-standing interest in biliary infections. We have characterized factors facilitating development of severe biliary infections, including advanced age, bacterial slime, bacterial cholangiovenous reflux and induction of TNFα production (most common with E. coli and Klebsiella spp.). Recognized signs of cholangitis include fever/chills, jaundice, RUQ pain, hypotension, and altered mental status. We noted several cases with findings of new onset fatigue or weakness (separate from altered mental status) associated with severe biliary infections. We, therefore, studied the association between new onset fatigue or weakness (FatigWeak) and severity of the biliary infection.

Methods: We studied 1090 VA patients with gallstone disease [967 (89%) men, average age 64 years]. Gallstones, bile, and blood (as applicable) were cultured. Severity of illness was classified: None (no infectious/ inflammatory manifestations), Systemic Inflammatory Response Syndrome (SIRS - fever, leukocytosis, tachycardia), Severe (abscess, cholangitis, empyema), or Sepsis-Multiple Organ Dysfunction Syndrome (MODS - bacteremia, hypotension, organ failure). New onset fatigue or weakness (FatigWeak) was identified and correlated with clinical findings.

Results: Biliary bacteria were present in 52%, bacteremia in 117/456 (26%) cases. FatigWeak was present in 122 cases; these patients were older (74 vs 62 years, p<0.001), harbored biliary bacteria, and more often had bacteremia (48% vs 19%, p< 0.001) (Fig 1). Cases with FatigWeak more often had cultures positive for E. coli or Klebsiella species (60% vs 42%, p<0.001). New onset FatigWeak was associated with increased illness severity (Sepsis-MODS: 81% vs 15%, p<0.001) (Fig 2). In 23% of FatigWeak cases, onset proceeded development of sepsis (days to months). Additionally, 20% of patients with FatigWeak symptoms had associated weight loss. Presentations varied: some patients underwent medical evaluation of weakness before identification (or manifestation) of their biliary infection; others called 911 when weakness progressed to near paralysis. In these patients, FatigWeak symptoms resolved following treatment of the biliary infection. We also reviewed Reynold's 1959 paper and noted that 1 of 6 cases he reported had weakness that preceded mental confusion and shock.

Conclusions: This study illustrates the important correlation between new onset fatigue or weakness and severe biliary infection, including biliary sepsis-MODS. FatigWeak was more common in cases with bacteremia, especially in those with E. coli and Klebsiella species. New onset FatigWeak could herald the development of biliary sepsis, emphasizing the need to consider biliary infection in these cases. This is the first paper to clearly show that FatigWeak is an important clinical indicator that can signify progression to cholangitis and MODS.






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